Although recent progress in brain protection during

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1 Prospective Comparative Study of Brain Protection in Total Aortic Arch Replacement: Deep Hypothermic Circulatory Arrest With Retrograde Cerebral Perfusion or Selective Antegrade Cerebral Perfusion Yutaka Okita, MD, Kenji Minatoya, MD, Osamu Tagusari, MD, Motomi Ando, MD, Kazuyuki Nagatsuka, MD, and Soichiro Kitamura, MD Department of Cardiovascular Surgery and Neurology, National Cardiovascular Center, Osaka, Japan Background. The purpose of this study was to compare the results of total aortic arch replacement using two different methods of brain protection, particularly with respect to neurologic outcome. Methods. From June 1997, 60 consecutive patients who underwent total arch replacement through a midsternotomy were alternately allocated to one of two methods of brain protection: deep hypothermic circulatory arrest with retrograde cerebral perfusion (RCP: 30 patients) or with selective antegrade cerebral perfusion (SCP: 30 patients). Preoperative and postoperative (3 weeks) brain CT scan, neurological examination, and cognitive function tests were performed. Serum 100b protein was assayed before and after the cardiopulmonary bypass, as well as 24 hours and 48 hours after the operation. Results. Hospital mortality occurred in 2 patients in the RCP group (6.6%) and 2 in the SCP group (6.6%). New strokes occurred in 1 (3.3%) of the RCP group and in 2 (6.6%) of the SCP group (p 0.6). The incidence of transient brain dysfunction was significantly higher in the RCP group than in the SCP group (10, 33.3% vs 4, 13.3%, p 0.05). Except in patients with strokes, S-100b values showed no significant differences in the two groups (RCP: SCP, prebypass : , postbypass : , 24 hours : , 48 hours : g/l, p 0.7). There were no intergroup differences in the scores of memory decline (RCP ; SCP , p 0.6), orientation (RCP ; SCP , p 0.08), or intellectual function (RCP ; SCP , p 0.7). Conclusions. Both methods of brain protection for patients undergoing total arch replacement resulted in acceptable levels of mortality and morbidity. However, the prevalence of transient brain dysfunction was significantly higher in patients with the RCP. (Ann Thorac Surg 2001;72:72 9) 2001 by The Society of Thoracic Surgeons Although recent progress in brain protection during surgery for the transverse aortic arch has been achieved, significant incidence of permanent or transient postoperative disorders of the central nervous system have remained a major unsolved problem. This study compared the results of two different methods of brain protection, deep hypothermic circulatory arrest with retrograde cerebral perfusion (RCP) and with selective antegrade cerebral perfusion (SCP), particularly with respect to the neurologic outcome in a prospective manner. Patients and Methods From June 1, 1997 to April 9, 1999, 84 patients had a total replacement of the transverse aortic arch in the National Accepted for publication March 27, Address reprint requests to Dr Okita, Department of Surgery, Division II, Kobe University School of Medicine , Kusunoki-cho, Chuo-ku, Kobe , Japan; yokita@med.kobe-u.ac.jp. Cardiovascular Center, Osaka, Japan. Seventeen patients who underwent an emergent surgery because of acute aortic dissection or rupture of the aneurysm were excluded. Two patients who had a total aortic arch replacement via a left thoracotomy were also excluded from the analysis. Sixty consecutive patients who had a total arch replacement via a midsternotomy on an elective basis were entered in the investigation. They were allocated alternately into two groups with different methods of brain protection: deep hypothermic circulatory arrest (DHCA) with retrograde cerebral perfusion (RCP: 30 patients) and selective antegrade cerebral perfusion (SCP: 30 patients). All operations were performed by two surgeons (Y.O., M.A.) alternatively. Endpoints of this study were (1) to assess postoperative functional status of the brain, (2) to review postoperative brain CT scans, and (3) to compare S-100 B values. Patient demographics were essentially similar in the two groups (Table 1). The whole aortic arch was replaced using quadrifurcated collagen or a gelatin-impregnated 2001 by The Society of Thoracic Surgeons /01/$20.00 Published by Elsevier Science Inc PII S (01)

2 Ann Thorac Surg OKITA ET AL 2001;72:72 9 BRAIN PROTECTION IN TOTAL AORTIC ARCH REPLACEMENT 73 Table 1. Patient Demographics DHCA RCP SCP p Value Male:female 24:6 25:5 0.7 Age (y) range (y) Aortic lesions 0.4 dissection 3 5 non-dissection TIA, CI history Carotid or vertebral stenosis CI cerebral infarction; DHCA RCP deep hypothermic circulatory arrest retrograde cerebral perfusion; SCP selective antegrade cerebral perfusion; TIA transient ischemic attack of the brain. woven Dacron graft. In order to avoid injury to the esophagus and left recurrent nerve, open distal anastomosis was performed consistently with complete transection of the descending aorta distal to the left subclavian artery. The cannulation site for arterial return was sought meticulously by a preoperative CT scan and by an intraoperative epiaortic or transesophageal scan. When moderate to severe atheromatous plaque or ulceration was detected in the ascending aorta or when the ascending aorta was dissected, femoral cannulation or additional cannulation into the right axillary artery with a femoral cannula was employed. However, reperfusion and rewarming was always achieved in an antegrade manner through the side branch of the graft. Retrograde cerebral perfusion was implemented after the initiation of total circulatory arrest at a nasopharyngeal temperature of less than 18 degrees. Electroencephalography was not performed. Continuous retrograde cerebral perfusion flow was required to maintain an internal jugular vein pressure of 15 to 20 mm Hg. After anastomosing the left common carotid artery to the secondary branches of the graft, antegrade cerebral and body perfusion was resumed through the 4th side branch of the graft and rewarming was started. This was followed by anastomosis of the brachiocephalic artery, proximal anastomosis to the ascending aorta and final anastomosis of the left subclavian artery. Our principle in selective antegrade cerebral perfusion included arterial cannulation performed with an ordinary arterial cannula in the right axillary artery or with a balloon-tipped cannula inserted directly in the brachiocephalic artery from inside the aortic arch, and in the left common carotid artery. The left subclavian artery was usually clamped, except in patients with a dominant left vertebral artery. Cerebral perfusion flow was maintained at 300 to 500 ml/min; the mean pressure in the superficial temporal artery ranged from 40 to 60 mm Hg, and the nasopharyngeal temperature ranged from 20 to 25 degrees. Monitoring of the perfusion pressure at the bilateral superficial temporal arteries was performed using standard methods. After anastomosing the ascending aorta to the graft, coronary circulation was started and arch vessels, the left subclavian artery, the left common carotid artery, and the brachiocephalic artery were anastomosed in that order. Concomitant operative procedures performed in the RCP group were aortocoronary bypass in 4 patients, aortic root replacement with cusp sparing in 2, replacement of abdominal aortic aneurysm in 1, and elephant trunk procedure in 1 patient. In the SCP group, simultaneous surgery consisted of elephant trunk procedure in 6 patients, aortocoronary bypass in 4, replacement of the descending aorta in 2, replacement of abdominal aortic aneurysm in 2, bypass operation for arterial occlusion in 2, and aortic root replacement with cusp sparing in 1 patient. Preoperative and postoperative ( postoperative days) brain CT scan was performed routinely. Preoperative and postoperative neurological examination was performed in all patients by a neurologist (K.N.). Any new lesions detected by CT or persistent neurologic deficit were defined as stroke. Transient brain dysfunction was defined as mild intellectual disturbance, loss of orientation with respect to time and place, personal characteristic change, or memory disturbance. Grading of the transient brain dysfunction was defined as mild (insomnia, restlessness, anxiety, euphoria, strange facial appearance, unexplained complaints), moderate (manicdepressive, disorientation, repetition, trying to remove intravenous or other lines), and severe (rejection of treatment, hallucination, wandering, struggling, persecution mania). Routine pre and postoperative neuropsychologic tests were performed in the wards. The test at pretest and posttest based on the Mini-Mental State Examination [1] and its modifications, consisted of the following: (1) Orientation to time (5 points); (2) Orientation to place (5 points); (3) Registration and recall of five objects (5 points); (4) Attention and calculation serial seven (5 points); and (5) Antegrade and retrograde repetition of the digits (5 points). Scoring of each test was performed according to achievement of the batteries. The posttest was administered after stabilization of the general status of the patients (at days postoperatively). Serum S-100b protein was assayed immediately before and immediately after cardiopulmonary bypass, 24 hours, and 48 hours after the operation. The protocol of this study was approved by the Research Committee, National Cardiovascular Center. All patients entered in this study gave their consent at the time of their admission. Mean values were expressed as average standard deviation. Statistical analysis was conducted by the 2 test, unpaired Student s t test, Kruskal-Wallis test, regression analysis, the Mann-Whitney test, Friedman test, and Wilcoxon signed rank test. All hypothesis testing was done with a 5% critical significance level. Results Total duration of the operation (RCP , SCP , p 0.03 minutes; p 0.03) and bypass time (175 58, minutes; p 0.03) were significantly longer in the SCP group. Duration of cardiac ischemia ( , minutes; p 0.6) and of circulatory

3 74 OKITA ET AL Ann Thorac Surg BRAIN PROTECTION IN TOTAL AORTIC ARCH REPLACEMENT 2001;72:72 9 arrest of the lower body ( , minutes; p 0.07) were similar. In the RCP group, the duration of the total circulatory arrest was minutes, and the duration of RCP was minutes. In the SCP group, the duration of SCP was minutes. (Table 2). The lowest nasopharyngeal temperature was C in the RCP group and C in the SCP group (p 0.04). The arterial cannulation site was the ascending aorta (RCP 11 patients: SCP 8 patients), femoral artery (18:15), or right axillary and femoral artery (1:7, p 0.07). Hospital mortality was noted in 2 patients in the RCP group (6.6%) and 2 patients in the SCP group (6.6%). The causes of death were preexisting severely depressed left ventricular function and liver cirrhosis in the RCP group and postoperative stroke and respiratory failure, and postoperative heart failure and bowel necrosis in the SCP group. New strokes occurred in 1 patient (3.3%) in the RCP group and in 2 patients (6.6%) in the SCP group (p 0.6). All three strokes were diagnosed as brain embolism by computed tomography. None of the patients with preexisting cerebrovascular problems had a new stroke. The first patient with a new stroke was a 75-year-old female who had an atherosclerotic arch aneurysm with thick thrombi, left main trunk disease and triple vessel coronary heart disease, thoracoabdominal aortic aneurysm, repaired abdominal aortic aneurysm, and chronic obstructive pulmonary disease (COPD). She underwent total arch replacement with RCP of 37 minutes and three coronary bypass grafts. Femoral arterial cannulation was employed and the total bypass time was 279 minutes. She woke up 15 hours after the operation, but left hemiparesis was detected. Computed tomography revealed a Table 2. Operative Data DHCA RCP SCP p Value Operation (min) ( ) ( ) ECC (min) ( ) ( ) Cardiac ischemia (min) (57 231) (39 330) Lower body CA (min) (29 96) (5 116) Total CA (min) a (29 96) RCP (min) (12 73) SCP (min) (63 241) Lowest NPT ( C) (15 19) (18 24) a Includes Retrograde Cerebral Perfusion time. Data in parentheses is range. CA circulatory arrest; DHCA RCP deep hypothermic circulatory arrest retrograde cerebral perfusion; ECC extracorporeal circulation; NPT nasopharyngeal temperature; SCP selective antegrade cerebral perfusion. Fig 1. Degree of transient central nervous system dysfunction and duration of total circulatory arrest. (CA circulatory arrest.) small low density area at the left internal capsule. She was discharged after 5 months of rehabilitation. The second patient with a new stroke was a 70-year-old male with atherosclerotic distal arch aneurysm, abdominal aortic aneurysm, peripheral arterial occlusive disease, and chronic obstructive pulmonary disease (COPD). He underwent total arch replacement with SCP. Ascending aorta cannulation was employed and total bypass time was 190 minutes. His postoperative course was complicated by acute myocardial infarction, pneumothorax, and large cerebral infarction of the left parietofrontal lobe. He never gained consciousness and died 7 months later. The third patient with a new stroke was a 77-year-old male with chronic aortic dissection. Three years previously, he underwent replacement of the ascending proximal arch because of acute type A aortic dissection. A gradual increase in size of the distal aortic arch made additional surgery necessary. He underwent total arch replacement and elephant trunk procedures in the descending aorta with SCP of 139 minutes. Femoral cannulation was employed and the total bypass time was 220 minutes. He woke up at 10 hours and was extubated at 15 hours after the operation and recovery was uncomplicated. However postoperative computed tomography revealed a small low density area in the right frontal lobe. He was discharged on postoperative day 31 without any neurologic signs. The prevalence of transient brain dysfunction was significantly higher in the RCP group (10, 33.3% vs 4, 13.3%, p 0.05). The degree of the transient brain dysfunction was severe in 4 (RCP 3: SCP 1), moderate in 3 (RCP 3: SCP 1), and mild in 6 of the patients (RCP 4: SCP 2, p 0.4). Strikingly, 5 out of 6 patients who had brain circulatory arrest for more than 50 minutes in the RCP group had transient brain dysfunction, and the dysfunction was moderate or severe in all 5 cases (p 0.005). A significant correlation was demonstrated between the degree of transient brain dysfunction and the duration of brain circulatory arrest (Fig 1) in the RCP group. There was a weak correlation between the duration of brain circulatory arrest and the peak S-100b (r

4 Ann Thorac Surg OKITA ET AL 2001;72:72 9 BRAIN PROTECTION IN TOTAL AORTIC ARCH REPLACEMENT 75 Table 3. Postoperative Data DHCA RCP SCP p Value Wake-up (h) ( ) ( ) Extubation (h) 9.7 ( ) a 8.4 ( ) a 0.4 ICU stay (days) 4.1 (2 68) a 3.9 (2 22) a 0.3 Hospital stay (days) 28.5 (20 45) a 30.1 (17 155) a 0.3 a Median value; range of the data in parentheses. DHCA RCP deep hypothermic circulatory arrest retrograde cerebral infusion; ICU intensive care unit; SCP selective antegrade cerebral perfusion. Fig 2. Relationship between the brain circulatory arrest and post ECC peak S-100b. (CA circulatory arrest; CNS central nervous system; ECC extracorporeal circulation.) 0.61, p 0.06, Fig 2), but no relation was found between the duration of brain circulatory arrest and the S-100b value at 48 postsurgery (r 0.12, p 0.8) in the RCP group. In the SCP group, no relationship was found between the duration of SCP and the peak S-100b (r 0.25, p 0.8) or the S-100b value at 48 hours after surgery (r 0.08, p 0.9). Nonneurological complications consisted of respiratory failure in 3, acute myocardial infarction in 2, postoperative bleeding in 2, acute renal failure in 1, liver failure in 1, and hoarseness in 1 of the patients in the RCP group. In the SCP group, other complications were bleeding in 2, respiratory failure in 2, acute renal failure in 2, acute myocardial infarction in 1, complete atrioventricular block in 1, postoperative low cardiac output syndrome in 1, gastrointestinal bleeding in 1, delayed cardiac tamponade in 1, bowel necrosis in 1, and hoarseness in 1 patient. Among survivors, postoperative wake-up time (time duration from entry in the ICU to first meaningful response to a verbal order), extubation time, stay in the ICU, and postoperative hospital stay showed no significant difference between the RCP and SCP groups (Table 3). Except in the patients with strokes, S-100b values showed no differences in the two groups (Fig 3). In the 3 patients who had a new stroke postoperatively, S-100b was significantly elevated at 2 days after surgery and remained high thereafter (Fig 4). In the 14 patients who had transient neurologic dysfunction, neither the peak value of S-100b nor the S-100b value 48 after surgery showed a significant difference compared with the values in normal patients (Fig 5). Scores of memory decline (RCP ; SCP , p 0.6), orientation (RCP ; SCP , p 0.2), calculation (RCP ; SCP , p 0.8), and whole tests (RCP ; SCP , p 0.12), were not significantly different in the RCP and SCP groups (Fig 6). However, patients who had transient neurologic dysfunction were likely to have a larger decline of memory (nondysfunction vs dysfunction : , p 0.05), but no significant difference between patients with and without dysfunction was found in orientation ( : , p 0.8) or calculation ( : , p 0.8, Fig 7). Comment Although brain complication remains a rare event after cardiac surgery, it is a major cause of postoperative mortality and morbidity in thoracic aortic surgery [2]. An alarming prevalence (1% to 83%) [3, 4] of postoperative neuropsychological dysfunction has been reported after cardiopulmonary bypass. Improvement of methods to assess the postoperative neuropsychiatric status has been achieved recently; however, there is no simple Fig 3. Transition of s-100 protein in selective cerebral perfusion (SCP) and retrograde cerebral perfusion (RCP) groups. Patients with postoperative stroke were excluded. (ECC extracorporeal circulation.)

5 76 OKITA ET AL Ann Thorac Surg BRAIN PROTECTION IN TOTAL AORTIC ARCH REPLACEMENT 2001;72:72 9 Fig 4. Transition of s-100 protein in patients with postoperative stroke and without. (ECC extracorporeal circulation.) method to determine the incidence or severity of brain injury after a cardiac operation. In this study, we performed a prospective comparative study of two different methods of brain protection, deep hypothermic circulatory arrest with retrograde cerebral perfusion or selective antegrade cerebral perfusion, in total aortic arch replacement. Patients who underwent emergent surgery or had acute aortic dissection were excluded. Patients who underwent a partial replacement of the aortic arch, proximal or distal, and patients who had a left thoracotomy were also excluded from this study. Very few reports [5] dealing with this matter have been published and none of the published studies was performed in a prospective manner. Recent reports indicated that the majority of permanent neurologic injuries were due to strokes resulting from embolic phenomena, and were not directly related to the method of cerebral protection used. In an autopsy study, Amarenco and colleagues [6] reported that the prevalence of ulcerated plaques in the aortic arch was 28% in 183 patients with cerebral infarcts and 20% in 56 patients with brain hemorrhage. Blauth and associates [7] demonstrated a direct correlation between age, severe arteriosclerosis of the ascending aorta, and atheroemboli. We [8] also found that age was a significant risk factor for stroke in the univariate analysis. The partial bypass perfusion technique for procedures involving the descending aorta was a significant predictor for postoperative stroke. Clamping the aortic arch for anastomosis, where the open anastomosis technique was not used, was demonstrated to be the strongest risk factor for stroke. Risk of cerebral embolism due to dislodgment of loose atheromatous plaque or mural thrombi steeply increased when a cross-clamp was applied at the involved portion of the aorta. Although Westaby and Katsumata [9] recommended the use of antegrade perfusion even through the left thoracotomy, cannulation in the ascending aorta was likely to dislodge mural thrombi or debris when the ascending aorta was involved in the aneurysm or atherosclerotic changes. Wareing and coworkers [10] modified their technique of cardiac procedures according to the findings of intraoperative echography; the modifications included alterations in the site of aortic cannulation, aortic clamping, attachment of the vein grafts, and cannulation for infusion of cardioplegia, and even the performance of hypothermic circulatory arrest without clamping the aorta. None of their 68 patients with significant atheromatous disease in whom modifications in technique were made suffered from stroke. Svensson and associates [11] used logistic regression analysis to evaluate 656 patients after aortic surgery using deep hypothermia with circulatory arrest. They reported that there were 44 permanent or transient strokes (7%) and that the multivariable determined predictors were a history of cerebrovascular disease, previous aortic surgery distal to the left subclavian artery, and cardiopulmonary bypass time. The occurrence of stroke was ob- Fig 5. Transition of s-100 protein in patients with postoperative transient CNS problems and without. Patients with postoperative stroke were excluded. (CNS central nervous system; ECC extracorporeal circulation.)

6 Ann Thorac Surg OKITA ET AL 2001;72:72 9 BRAIN PROTECTION IN TOTAL AORTIC ARCH REPLACEMENT 77 Fig 6. Postoperative decline of the neuropsychiatric test. Selective cerebral perfusion (SCP) versus retrograde cerebral perfusion (RCP). served to increase after 40 minutes of circulatory arrest, and the mortality rate increased markedly after 65 minutes of circulatory arrest. Borst and colleagues [12] reported an early mortality of 10%, and 3 cerebral deaths among 58 atherosclerotic aneurysms treated using deep hypothermic circulatory arrest since Ergin and coworkers [13] reported that the mortality rate in patients without any neurologic injury was 6.7%, whereas in patients with permanent neurologic deficit the hospital mortality rate was 46%. The retrograde cerebral perfusion technique provides a new approach that can augment cerebral protection during circulatory arrest [14]. Coselli and LeMaire [15] reported that patients who had RCP during DHCA had lower mortality (7.9%) and stroke (2.4%) rates than those who did not undergo DHCA with RCP (early mortality 14.8%, stroke 6.5%) in their 479 patients. Safi and associates [16] demonstrated that the use of retrograde cerebral perfusion had a protective effect against stroke (3 of 120 patients, or 3%) compared with no retrograde cerebral perfusion (4 of 41 patients, or 9%). The protective effect was most significant in patients more than 70 years of age; none of their 36 elderly patients who received retrograde cerebral perfusion had a stroke, compared with 3 of the 13 (23%) who did not (p 0.003). Bavaria and Pochettino [17] reported that RCP may extend the safe HCA period and improve morbidity and mortality, especially when HCA times are longer than 60 minutes. Kitamura and colleagues [18] also reported improved clinical results using RCP compared with SCP. In our previous experience [19] with 148 consecutive patients who had RCP and DHCA, 15 (10%) early deaths and 6 new strokes (4.0%) occurred. RCP is clearly effective in maintaining cerebral hypothermia, providing continuous cooling of the whole head, preventing debris and air from reaching the terminal vessels of the brain, and in washing out some metabolites and thus delaying the onset of acidosis in the ischemic brain. In published reports of the SCP from Western countries about the use of SCP, Bachet and coworkers [20] reported that the operative mortality was 13%, and that 3 serious neurologic complications were found among 54 patients. Another French study by Le Mee and associates [21] using SCP reported a 13% early death rate and 10% stroke rate in 23 patients. Grabenwoger and associates [22] reported on combined use of DHCA and selective antegrade brachiocephalic perfusion in 105 patients. In reports regarding the use of SCP in Japan, although the number of patients was small, Kazui and colleagues [23] also demonstrated excellent surgical results with no neurologic sequelae and 3 early deaths in 32 patients with arch aneurysm. Tabayashi and associates [24] reported an early mortality of 11% and a 19% rate of stroke after aortic arch repair using selective cerebral perfusion in patients with atherosclerotic aneurysms. A Japanese multicenter combined study reported by Hayashi and associates [25] using SCP only for atherosclerotic aortic arch aneurysm revealed that age, aneurysmal rupture, Fig 7. Postoperative decline of the neuropsychiatric test. Transient CNS dysfunction versus normal. (CNS central nervous system.)

7 78 OKITA ET AL Ann Thorac Surg BRAIN PROTECTION IN TOTAL AORTIC ARCH REPLACEMENT 2001;72:72 9 and renal dysfunction were significant predictors of mortality and disability. The most important advantage of SCP is that it provides the luxury of time, allowing for deliberate repair of complicated arch aneurysms. However, there have been several criticisms against SCP, including the longer time required for arch repair, as well as cannulation-origin embolism, and uneven distribution of intracranial blood flow. Using SCP in 60 patients with atherosclerotic arch aneurysm, Ohmi and coworkers [26] reported a higher prevalence of postoperative stroke in patients with occlusive arterial disease, especially in emergency cases in which the status of cerebral circulation is unknown. However, the higher prevalence of transient neurologic deficit indicated the need for caution against overly liberal use of RCP. Our previous report [19] and this study demonstrated that some correlation exists between the severity of transient neurologic dysfunction and the duration of the brain circulatory arrest. Ergin and colleagues [13] showed that temporary neurologic dysfunction occurred in 19% of patients who underwent arch surgery using deep hypothermic circulatory arrest. Close correlation between the duration of arrest and cerebral injury, and especially a steep rise in the incidence of temporary dysfunction beyond 50 minutes of arrest time were demonstrated. Reich and associates [5] also reported that deep hypothermic circulatory arrest of 25 minutes or more and advanced age were associated with memory and fine motor deficits and with a prolonged hospital stay. Recent clinical applications of serum S-100b [27, 28] to evaluate postcardiotomy neuropsychiatric dysfunction demonstrated a positive correlation of the serum level of S-100b with the degree of brain injury and with duration of the cardiopulmonary bypass. Our data also demonstrated that elevated and prolonged elevation of the S-100b value occurred in patients with stroke or moderate or severe transient neurologic dysfunction. Wimmer- Greinecker [4] and colleagues reported that even when postoperative cognitive test scores were not significantly decreased as compared to preoperative values, S100b protein increased markedly during and immediately after coronary bypass surgery. Cerebral microemboli or micronecrosis have been demonstrated to be associated with neurocognitive dysfunction after cardiac surgery. The cause of this dysfunction may be small but numerous areas of focal cerebral ischemia. S-100b is a promising marker for cerebral injury in cardiac surgery if elevated levels of it can be linked with the clinical outcome. Certain limitations existed in evaluating the postoperative results of the neuropsychiatric tests. The main limitation was that the test was not simple enough for recovering patients to answer on the 10th postoperative day. The sickest patients were not able to do the tests, because usually they were intubated, sedated, and on a ventilator in the intensive care unit. However, a significant postoperative decline of memory function in patients with transient cerebral dysfunction was demonstrated. A prospective comparative study of two different methods of brain protection, with evaluation including a cognitive function test, was performed in patients who underwent total arch replacement. 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